个人介绍:
日本东京农工大学获得博士学位,美国宾西法尼亚州立大学博士后研究员。威尼斯wnsr666教授,博士生导师,生命科学学位分会主席,蛋白质与基因研究国家重点实验室副主任。担任国家自然科学基金医学科学领域学科评审组成员,北京市自然科学基金生物学科组会议评审专家。中国生物化学与分子生物学会蛋白质专业委员会委员,中国生物化学与分子生物学会酶学专业委员会委员、常务委员,中国生物物理学会女科学家分会理事。北京市生物化学与分子生物学学会副理事长。
研究组主要利用生化分子生物学、细胞生物学、免疫学和结构生物学等技术方法,鉴定新的调控肿瘤细胞生长、炎症和固有免疫性疾病的蛋白,包括影响肿瘤转移和耐药的外泌体蛋白,研究这些蛋白发挥作用的信号通路和分子机制。探讨泛素化、类泛素化和磷酸化等蛋白质翻译后修饰在DNA 损伤应答、炎症、肿瘤发生发展中的调控作用及机制,明确蛋白质功能的失调与炎症、肿瘤等重大疾病的发生和发展的关系。
先后主持、承担了20余项国家自然科学基金重点项目、面上项目,国际合作ICGEB课题,教育部博士点基金和优先发展基金、国家“重大科学研究计划”课题,科技部863课题、973课题等多项课题的研究。已经发表多篇SCI文章,其中作为通讯作者发表了68篇文章(Nature Comm,Cell Death Differentiation,PNAS, PLoS Pathogen, Oncogene, Nucleic Acid Res, Cell Res, J Cell Sci, JBC等),合作发表包括Science和PNAS等在内的16篇SCI论文,作为第一作者发表6篇文章。
教育经历:
1994 - 1998 , 理学博士 , 生化与分子生物学 , 东京农工大学
工作经历:
2008年6月 - 至今 , 教授 , 威尼斯wnsr666 威尼斯wnsr666
2002年5月 - 2008年5月 , 副教授 , 威尼斯wnsr666 威尼斯wnsr666
1998年4月 - 2002年4月, 博士后研究员 , 美国 宾夕法尼亚州大学
社会服务工作:
2014年-至今,任威尼斯wnsr666学位委员会委员、研究生教育委员会委员。
2012年-至今,任2012级研究生2班班主任工作。
荣誉奖励:
Bayer学者奖,2020
威尼斯wnsr666优秀博士学位论文指导教师,2020
威尼斯wnsr666优秀教学奖,2017
威尼斯wnsr666优秀班主任,2016
威尼斯wnsr666优秀博士学位论文指导教师,2016
威尼斯wnsr666优秀博士学位论文指导教师,2014
威尼斯wnsr666东宝教师奖 , 2013
威尼斯wnsr666东宝教师奖 , 2009
威尼斯wnsr666青年教师教学基本功优秀奖 , 2007
威尼斯wnsr666东宝教师奖 , 2006
北京市优秀辅导员 , 2006
谈家桢基金生命科学九源导师奖 , 2006
威尼斯wnsr666优秀班主任 , 2005
学术任职:
2021年- 中国生物化学与分子生物学会蛋白质专业委员会委员
2018年- 中国生物化学与分子生物学会理事
2016年- 北京生物化学与分子生物学会 副理事长
2015年-至今 中国生物物理学会女科学家分会理事
2015年-至今 中国生物化学与分子生物学会酶学专业委员会委员、常务委员
2005年-至今 中国细胞生物学会会员
2003年-至今 中国生物物理学会会员
2003年-至今 中国生物化学与分子生物学会会员
1998年-至今 美国生物化学学会会员评审任职:
2005年-至今 中国博士后基金 评审专家
2006年-至今 国家自然科学基金生命学部 评审专家
2006年-至今 山东省自然科学基金生命科学 评审专家
2015年-至今 国家自然科学基金医学科学领域学科评审组成员,
2015年-至今 北京市自然科学基金生物学科组会议评审专家,
2017年-至今 国家自然科学基金生命科学领域学科评审组成员。
会议发言与组织:
2022-12-10 13th International symposium on DNA Damage Response and Human Diseases. 大会报告
2021-12-11 The 2nd Xi An International Translational Medicine Symposium 大会报告
2021-11-22~11-25 The Third Cold Spring Harbor Conferences Asia Meeting 大会报告
2020-10-30-11-1 第九届中国乳腺癌干细胞高峰论坛 大会报告
2019-11-9~11-10 10th International symposium on DNA Damage Response and Human Diseases. 中国深圳大会报告
2019-06-12~6-13 6th Macau Symposium on Biomedical Sciences 大会报告
2018-06-11~6-15 Cold Spring Harbor Meeting 2018.DNA METABOLISM, GENOMIC STABILITY
& HUMAN DISEASE 大会报告
2017 12-02~12-03 南方科技大学国际肿瘤转化医学高峰论坛,中国深圳大会报告
2017 12-01~12-02 第六届广州国际肿瘤学会议,中国广州大会报告
2017 10-27~10-29 8th International symposium on DNA Damage Response and Human Diseases. 中国深圳大会报告
2017 09-21~09-24 第六届广州跨学科蛋白质研究会议,中国广州大会报告
2017 08-18~08-21 第十三届全国酶学学术讨论会,中国长春大会报告
2017 05-27~05-29 Cullin RING ligases and Protein NEDDylation:Biology and Therapeutics.中国杭州大会报告
2017 05-12~05-14 中华医学会医学细胞生物学分会第六次全国学术大会中国西安大会报告.
2016 06-24~06-26 The Second Trilateral Workshop for Frontier Protein Studies. 日本 大阪
大会报告
2016-10-21~10-23 8th International Conference SUMO, Ubiquitin, UBL Proteins:Implications for Human Diseases中国 上海
大会报告:hCINAP, a novel regulator of ubiquitin-like protein modifications in various signaling pathways, is essential for tumor growth
中美肿瘤论坛, 大会报告:hCINAP, an atypical enzyme, is a novel player in tumorigenesis.哈尔滨,2016.1.15-17.
第十四次中国暨国际生物物理大会,分会报告:Human NADPH sensor HSCARG plays important roles in fundamental cellular processes.昆明,2015-11-17.
第十二届全国酶学学术讨论会,大会报告:腺苷酸激酶hCINAP的结构和功能研究。威海,2015-9-19.
2015蛋白质修饰与降解论坛,大会报告:组蛋白H2A泛素化、类泛素化修饰调控的新机制,上海,2015.6.
The Seventh International Conference SUMO, Ubiquitin, UBL Proteins: Implications for Human Diseases.大会报告: HSCARG Negatively Regulates the Cellular Antiviral RIG-I Like Receptor Signaling Pathway by Inhibiting TRAF3 Ubiquitination via Recruiting OTUB1. 上海,2014.5.
中国生物化学与分子生物学会第十一届会员代表大会暨2014年全国学术会议,RNF168-mediated H2A neddylation antagonizes its ubiquitination and regulates DNA damage repair. 厦门,2014.8.
2012年全国生物化学与分子生物学学术大会,报告题目:hCINAP is a novel regulator of ribosomal protein-HDM2-p53 pathway via controlling NEDDylation of ribosomal protein S14成都, 2012.8.
The 17th IBC (IUPAB). 报告题目:Structural insight into the regulatory mechanism of human UDP-glucose pyrophosphorylase,北京,2011.10.
中国细胞生物学学会第十二次全体会员代表大会暨学术大会. 报告题目:Crystal structure of PACSIN F-BAR domain reveals a novel membrane curvature sensing mechanism.北京,2011.7.
The Inaugural Xiamen Winter Symposium “Molecular Mechanisms and Signalling in Cancer Biology”,报告题目:USP7 deubiquitinates NEMO through the interaction with HSCARG,厦门,2011.2.
2010年中国生物化学与分子生物学会第十届全国会员代表大会暨全国学术会议. 报告题目:Crystal structure of PACSIN F-BAR domain reveals a novel membrane curvature sensing mechanism. 南京,2010.8.
第三届中国结构生物学学术讨论会,报告题目:人类分泌蛋白SI-CLP通过巨噬细胞调节固有免疫反应,三亚,2010.3.
21st IUBMB and 12th FAOBMB International Congress of Biochemistry and Molecular Biology(第21届国际生物化学与分子生物学联盟学术大会暨第12届亚洲大洋洲生物化学家与分子生物学家学术大会),上海,2009.8.
2009年北京同步辐射装置用户学术年会暨专家会,分会报告:NADPH是HSCARG的变构调节因子,分会报告,太原,2009.8.
10th Sino-Singapore Symposium in Biology,大会报告:HSCARG inhibits activation of NF-κB by interacting with IκB kinase-β. 厦门,2009.11.
第二届全国“跨学科蛋白质研究”学术讨论会,NADPH sensor protein HSCARG down-regulates NO synthesis and is essential for cell viability. 烟台,2008.7.
北京生物化学学会2007年年会 , 2007.12
International Symposium on Synchrotron Radiation and Biology, Restructuring of the dinucleotide binding fold in a NADP(H) sensor protein, 上海,2007.11
Serum presence of preS antigen in chronic hepatitis B: a significant serological marker in HBV prognosis,Advances in Protein Sciences, Hongkong , 2005.12
Activation of the protein kinase PKR by small double-stranded RNAs flanked by single-stranded regions.,The 3rd Annual Meeting of the China RNA Society & 1st International RNA Workshop in China , 2003.7
Straightening of bulged RNA by the double-stranded RNA-binding domain from the protein kinase PKR,Second International Conference: Proteins that bind RNA , 2001.2
杂志编辑:
2012年-至今 World Journal of Biological Chemistry 编委
2022年-至今 ABBS(生物化学与生物物理学报)编委教材编撰:
现代分子生物学(第5版),高等教育出版社,朱玉贤,李毅,郑晓峰,郭红卫执教课程:
基础分子生物学 , 主讲, 威尼斯wnsr666, 秋季、2004-至今
研究生科研规范训练,主持,威尼斯wnsr666, 秋季、2014-至今
蛋白质的翻译后修饰及其调控作用,主持, 威尼斯wnsr666, 春季、2015-
现代生物学实验技术原理及其应用,主持, 威尼斯wnsr666, 秋季、2015-
生化与分子生物学进展,主讲,威尼斯wnsr666, 秋季、2006-至今
蛋白质晶体学,主讲,威尼斯wnsr666, 秋季、2012-2014
一些参与基本生物学过程的重要蛋白质的功能失调会影响细胞的正常生理功能,并可能导致炎症、肿瘤在内的多种疾病,因此,对这些蛋白的结构和功能开展研究具有重要的生物学意义。我们实验室利用生化分子生物学、细胞生物学、免疫学和结构生物学等技术方法,发现并鉴定调控肿瘤细胞生长、炎症和固有免疫性疾病的新的调控蛋白,研究这些蛋白发挥作用的信号通路和分子机制。研究泛素化、类泛素化和磷酸化等蛋白质翻译后修饰在DNA 损伤应答、炎症、肿瘤发生发展中的调控作用及机制,明确蛋白质功能的失调与炎症、肿瘤等重大疾病的发生和发展的关系。
本实验室主要兴趣在于:
1. 肿瘤发生发展和转移调控蛋白的筛选、鉴定和分子机制研究
2. DNA损伤修复—基因组稳定性----癌症
3. 病毒--固有免疫—DNA损伤应答—炎症和肿瘤
1.Fu JF, Zhou SR, Xu HL, Liao LM, Shen H, Du P, Zheng XF*. (2023) ATM-ESCO2-SMC3 axis promotes 53BP1 recruitment in response to DNA damage and safeguards genome integrity by stabilizing cohesin complex. Nucleic Acids Res. 51(14)7376-7391.
2.Liao LM, Xu HL, Zhao YH, Zheng XF*. (2023) Metabolic Interventions Combined with CTLA-4 and PD-1/PD-L1 Blockade for the Treatment of Tumors: Mechanisms and Strategies. Frontiers of Medicine. 17(5): 805−822. (Review article).
3.Wei M, Huang XP, Liao LM, Tian YL, Zheng XF*. (2023) SENP1 decreases RNF168 phase separation to promote DNA damage repair and drug resistance in colon cancer. Cancer Research. 83(17):2908-2923.
4.Huang XP, Zhao Y, Wei M, Zhuge RP, Zheng XF*. (2023) hCINAP alleviates senescence through regulating MDM2 status via multiple mechanisms. Journal of Molecular Cell Biology.
Doi: 10.1093/jmcb/mjad015.
5.Zhuge RP, Wang C, Wang J, Yu SY, Liao LM, Zheng XF*. (2023) hCINAP controls lineage differentiation of embryonic stem cells by regulating NEDD4 liquid-liquid phase separation-mediated YAP1 activation. Cell Reports..42(1) 111935. (Jan 31 2023, https://doi.org/10.1016/j.celrep.2022.111935)
6.Huang XP, Yang YF, Zhu D, Zhao Y, Wei M, Li K, Zu HH. Zheng XF*. (2022) PRMT5-mediated RNF4 methylation promotes therapeutic resistance of APL cells to As2O3 by stabilizing oncoprotein PML-RARα. Cellular and Molecular Life Sciences. 79:319
7.Zhao Y, Huang XP, Zhu D, Wei M, Yu SY, Tian YL, Zheng XF*. (2022) Deubiquitinase OTUD6A promotes breast cancer progression by increasing TopBP1 stability and rendering tumor cells resistant to DNA-damaging therapy. Cell Death & Differentiation. 29: 2531–2544. Doi: 10.1038/s41418-022-01036-6.
8.Yu SY, Zang WC, Oiu YC, Liao LM, Zheng XF*. (2022) Deubiquitinase OTUB2 exacerbates the progression of colorectal cancer by promoting PKM2 activity and glycolysis. Oncogene. 41(1):46-56. DOI:10.1038/s41388-021-02071-2.
9.Xu RD, Yang YF, Zheng XF*. (2021) Unique structural features of the adenylate kinase hCINAP/AK6 and its multifaceted functions in carcinogenesis and tumor progression. FEBS Lett. 595(16): 2071-2084. DOI: 10.1002/1873-3468.14158
10.Zhu D, Xu R, Huang X, Tang Z, Tian Y, Zhang J, Zheng XF*. (2021) Deubiquitinating enzyme OTUB1 promotes cancer cell immunosuppression via preventing ER-associated degradation of immune checkpoint protein PD-L1. Cell Death & Differentiation. 28:1773–1789. Doi: 10.1038/s41418-020-00700-z.
11.Yang YF, Yang CZ, Li TT, Yu SY, Cui J, Zheng XF*. (2020) The deubiquitinase USP38 promotes NHEJ repair through regulation of HDAC1 activity and regulates cancer cell response to genotoxic insults. Cancer Res. 80 (4): 719-731. Dec 24 (online). Doi:10.1158/0008-5472.CAN-19-2149.
12.Zang WC & Zheng XF*. (2020) Structure and Functions of cellular redox sensor HSCARG/NMRAL1, a linkage among redox status, innate immunity, DNA damage response, and cancer. Free Radical Biology and Medicine. 160: 768-774.
13.Zang WC, Yang CZ. Li TT, Liao LM, Zheng XF*. (2019) Cellular redox sensor HSCARG negatively regulates the translesion synthesis pathway and exacerbates mammary tumorigenesis. Proc.Natl.Acad.Sci.USA. December 17, 116 (51): 25624-25633. https://doi.org/10.1073/pnas.1910250116
14.Xu RD, Yu SY, Zhu D, Huang XP, Lao YM, Zhang JF, Tang ZF, Zhang ZM, Yi J, Zhu HH, Zhu, Zheng XF*. (2019) hCINAP regulates the DNA damage response and mediates the resistance of acute myelocytic leukemia cells to therapy. Nature Communications.10,3812. Doi.org/10.1038/s41467-019-11795-5.
15.Yang CZ, Zang WC, Ji YP, Li TT, Yang YF, Zheng XF*. (2019) Ribosomal protein L6 (RPL6) is recruited to DNA damage sites in a poly(ADP-ribose) polymerase-dependent manner and regulates the DNA damage response. J Biol Chem. 294(8): 2827-2838. Doi: 10.1074/jbc.RA118.007009
16.Guan JH, Zheng XF*. (2019) NEDDylation regulates RAD18 ubiquitination and localization in response to oxidative DNA damage. Biochemical Biophysical Research Communications. 508: 1240-1244. Doi.org/10.1016/j.bbrc.2018.12.072.
17.Yang CZ, Zang WC, Tang ZF, Ji YP, Xu RD, Yang YF, Luo AP, Hu B, Zhang ZM, Liu ZH, Zheng XF*. (2018) A20 regulates the DNA damage response and mediates tumor cell resistance to DNA damaging therapy. Cancer Research. 78(4): 1069-1082. Doi: 10.1158/0008-5472.CAN-17-2143.
18.Guan JH, Yu SY, Zheng XF*. (2018) NEDDylation antagonizes ubiquitination of proliferating cell nuclear antigen and regulates the recruitment of polymerase η in response to oxidative DNA damage. Protein Cell. 9(4):365-379. DOI 10.1007/s13238-017-0455-x.
19.Ji YP, Yang CZ, Tang ZF, Yang YF, Tian YL, Yao HW, Zhu X, Zhang ZM, Ji JF, Zheng XF*. (2017) Adenylate kinase hCINAP determines self-renewal of colorectal cancer stem cells in a glycolysis-dependent manner by facilitating LDHA phosphorylation. Nature Communications. 8:15308. Doi.10.1038/ncomms15308.
20.Dong XD, Guan JH, Zheng CF, Zheng XF*. (2017, May 19) The herpes simplex virus 1 UL36USP deubiquitinase suppresses DNA repair in host cells via deubiquitination of proliferating cell nuclear antigen. J Biol Chem. 292 (20): 8472-8483. DOI 10.1074/jbc.M117.778076.
21.Bai DM, Zheng XF*. (2017) PML-RARA mutations confer varying arsenic trioxide resistance. Protein & Cell. 8(4):296–301. DOI: 10.1007/s13238-016-0356-4.
22.Yan FX, Guan JH, Peng YY, Zheng XF*. (2017) MyD88 NEDDylation negatively regulates MyD88-dependent NF-κB signaling through antagonizing its ubiquitination. Biochemical and Biophysical Research Communications. 482 (4): 632-637.
23.Bai DM, Zhang J, Li T, Hang R, Liu Y, Tian Y, Huang D, Qu L, Cao XF, Ji J-F, Zheng XF*. (2016) The ATPase hCINAP regulates 18S rRNA processing and is essential for embryogenesis and tumor growth. Nature Communications.7: 12310.
24.Qu LL, Ji YP, Zhu X, Zheng XF*. (2015) hCINAP Negatively Regulates NF-κB Signaling by Recruiting the Phosphatase PP1 to Deactivate IKK Complex. Journal of Molecular Cell Biology. 7 (6): 529-542. doi: 10.1093/jmcb/mjv041.
25.Liu Y, Yang YF, Fan JL, He RN, Luo M, Zheng XF*. (2015) The Crystal Structure of PB2 Cap-binding Domain of Influenza B Virus Reveals a Novel Cap Recognition Mechanism. J Biol. Chem. 290(14): 9141-9149.
26.Li TT, Guan J, Li SZ, Zhang XD, Zheng XF*. (2014) HSCARG downregulates TNF-induced NF-κB signaling by interacting with USP7 and inhibiting NEMO ubiquitination. Cell Difference & Diseases.5: e1229. Doi: 10.1038/cddis.2014.197.
27.Hu B, Li SZ, Zhang XD, Zheng XF*. (2014) HSCARG, a novel regulator of H2A ubiquitination by downregulating PRC1 ubiquitin E3 ligase activity, is essential for cell proliferation. Nucleic Acid Res. 42, 5582-5593
28.Li G, Qu L, Ma S, Wu Y, J CW, Zheng XF*. (2014) Structures determination of human Fas Apoptosis Inhibitory Molecule and identification of the critical residues linking the interdomain interaction to the anti-apoptotic activity. Acta crystallographica section D. D70, 1812-1822.
29.Peng YY, Xu RD, Zheng XF*. (2014) HSCARG negatively regulates the cellular antiviral RIG-I like receptor signaling pathway by inhibiting TRAF3 ubiquitination via recruiting OTUB1. PLoS Pathogens. 10(4): e1004041.
30.Li TT, Guan JH, Huang ZJ, Hu X, Zheng XF*. (2014) RNF168-mediated H2A neddylation antagonizes its ubiquitination and regulates DNA damage repair. J Cell Sci. 127: 2238-2248.
31.Zhang JF, Bai DM, Ma XW, Guan JH, Zheng XF*. (2014) hCINAP is a novel regulator of ribosomal protein-HDM2-p53 pathway by controlling NEDDylation of ribosomal protein S14. Oncogene. 33, 246-254. doi: 10.1038/onc.2012.560.
32.Xiao W, Meng G, Zhao Y, Yuan H, Li T, Peng Y, Zhao Y, Luo M, Zhao, WM, Li Z, Zheng XF*. (2014) Human secreted stabilin-1-interacting chitinase-like protein aggravates the inflammation associated with rheumatoid arthritis and is a potential macrophage inflammatory regulator in rodents. ARTHRITIS & RHEUMATOLOGY. 66(5):1141-1152.
33.Bai DM, Zhang J, Xiao WC, Zheng XF*. (2014) Regulation of the HDM2-p53 pathway by ribosomal protein L6 in response to ribosomal stress. Nucleic Acid Res. 42(3):1799-1811.
34.Meng G, An X, Ye, S, Liu Y, Zhu W, Zhang R, Zheng XF*. (2013) The crystal structure of LidA, a translocated substrate of the Legionella pneumophila Type IV secretion system, reveals a novel folding. Protein & Cell. 4(12):897-900.
35.Bai XY, Zheng XF*. (2013) Tip-to-tip interaction in the crystal packing of PACSIN 2 is important in regulating tubulation activity. Protein & Cell. 4(3): 211–219.
36.Xiao WC, Peng YY, Liu Y, Li Z, Li SL, Zheng XF*. (2013) HSCARG inhibits NADPH oxidase activity through regulation of the expression of p47phox. PLoS One. 8(3): e59301.
37.Liu Y, Qin K, Meng G, Zhang J, Zhou JF, Zhao GY, Luo M, Zheng XF*. (2013) Structural and Functional Characterization of K339T Substitution Identified in the PB2 subunit Cap-binding Pocket of Influenza A Virus. J Biol. Chem. 288(16): 11013-11023.
38.Liu Y, Meng G, Luo M, Zheng XF*. (2013) Crystallization and X-ray crystallographic analysis on the cap binding domain of influenza A virus H1N1 polymerase subunit PB2. Acta crystallgrophy F. 69: 280-283.
39.Feng X, Yang R, Zheng XF*, Zhang F. (2012) Identification of a novel nuclear-localized adenylate kinase 6 from Arabidopsis thaliana as an essential stem growth factor. Plant Physiol Biochem. 61: 180-186.
40.Bai X, Meng G, Luo,M, Zheng XF*. (2012) Rigidity of the Wedge Loop in PACSIN 3 is a Key Factor in Dictating the Diameters of Tubules. J Biol. Chem. 287(26):22387-22396.
41.Zhang M, Hu B, Li T, Peng Y, Guan J, Lai S, Li Z, Zheng XF*. (2012) A CRM1-dependent nuclear export signal controls nucleocytoplasmic translocation of HSCARG, which regulates NF-κB activity. Traffic. 13(6):790-799.
42.Yu Q, Zheng XF*. (2012) The crystal structure of human UDP-glucose pyrophosphorylase reveals a latch effect important for regulating pyrophosphorylase activity. Biochemical J. 442(2): 283-291.
43.Bai X, Meng G, Zheng XF*. (2012) Cloning, purification, crystallization and preliminary X-ray diffraction analysis of mouse PACSIN 3 protein from Escherichia coli. Acta crystallgrophy F68, 159-162.
44.Zhu WZ, Meng G, Liu Y, Zhang FY, Zheng XF* (2011) Protein Expression, Crystallization and Preliminary X-Ray Crystallographic Studies on LidA from Legionella pneumophila. Acta crystallgrophy F67, 637-639.
45.Li GM, Qiang Chen, Dai KS, Zheng XF*. (2011) The Ca2+-dependent multimerization of Homo sapiens S100 domain in Cornulin protects cells from injury. Progress in Biochemistry and Biophysics. 38(3): ~9.
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主要研究方向包括鉴定影响肿瘤发生发展和转移调控的新蛋白,揭示泛素化、类泛素化、乙酰化等蛋白质翻译后修饰在DNA损伤应答、肿瘤细胞耐药、肿瘤代谢、免疫调控中的作用和分子机制。先后主持和承担了国家自然科学基金生命学部和医学部重点项目(3)、面上项目(7),国际合作ICGEB课题(2),教育部博士点优先发展基金、科技部863、973、国家重大科学研究计划近二十个项目的研究。
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